DNA from fecal immunochemical test can replace stool for detection of colonic lesions using a microbiota-based model

Abstract

Background: There is a significant demand for colorectal cancer (CRC) screening methods that are noninvasive, inexpensive, and capable of accurately detecting early stage tumors. It has been shown that models based on the gut microbiota can complement the fecal occult blood test and fecal immunochemical test (FIT). However, a barrier to microbiota-based screening is the need to collect and store a patient's stool sample.

Results: Using stool samples collected from 404 patients, we tested whether the residual buffer containing resuspended feces in FIT cartridges could be used in place of intact stool samples. We found that the bacterial DNA isolated from FIT cartridges largely recapitulated the community structure and membership of patients' stool microbiota and that the abundance of bacteria associated with CRC were conserved. We also found that models for detecting CRC that were generated using bacterial abundances from FIT cartridges were equally predictive as models generated using bacterial abundances from stool.

Conclusions: These findings demonstrate the potential for using residual buffer from FIT cartridges in place of stool for microbiota-based screening for CRC. This may reduce the need to collect and process separate stool samples and may facilitate combining FIT and microbiota-based biomarkers into a single test. Additionally, FIT cartridges could constitute a novel data source for studying the role of the microbiome in cancer and other diseases.

Keywords: Colorectal cancer; Fecal immunochemical test; Gut microbiome; Microbiota; Random forest.

Fig. 1

Bacterial community structure from FIT cartridge recapitulates stool. Density plots showing distribution of the number of shared OTUs (a) and community similarity (b) between groups of samples (*p < 0.001 two-sample Kolmogorov-Smirnov test)

Fig. 2

Bacterial populations conserved between stool and FIT cartridge. a Scatter plot of the average relative abundance of each bacterial genus in stool and FIT cartridges colored by phylum. b Scatter plots of the relative abundances of the four species frequently associated with CRC. All correlations were greater than 0.35 (all p < 0.001)

Fig. 3

Microbiota-based models from FIT cartridge DNA are as predictive as models from stool. a ROC curves for distinguishing healthy patients from those with cancer using microbiota-based random forest models using DNA from FIT cartridges or stool. b Probability of having cancer for each patient according to microbiota-based models from a. c ROC curves for distinguishing patients with adenomas or carcinomas from healthy patients using microbiota-based random forest models using DNA from FIT cartridges or stool. d Probability of having a lesion for each patient based on the models from c